Correlation of angiotensin converting enzyme gene polymorphism with perioperative myocardial protection under extracorporeal circulation

Objective:To observe the expression of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),cardiac troponin 【cTnⅠ),creatine kinase isozymes(CK-MB) and muscle red protein(Myo) after cardiopulmonary bypass(CPB),and to investigate the association of polymorphisms in angiotensin converting enzyme genes and myocardial injury.Methods:Sixty-three patients suffered from rheumatic mitral stenosis and scheduled for mitral valve replacement with CPB, were randomly divided into three groups according polymorphisms in angiotensin converting enzyme genes:typeⅡ,type ID,type DD(each=21).Blood samples were withdrawn from artery before operation(T1),at the beginning of CPB(T2),30 min after CPB(T3),(T4) at the end of CPB(T5), 2 h after CPB(T6),6 h after CPB(17) to measure the expression of ACE,AngⅡ,cTnⅠ,CK-MB, Myo.Results:The level of ACE during and after CPB were significantly higher than those before CPB(P【0.05).As extension of CPB time,the expression of ACE was increased.The level of cTnⅠ, CK-MB,Myo after CPB were significantly higher than those before CPB(P【0.05).The level of cTnⅠ,CK-MB and Myo were highest at T7,T6 and T5 and T7,respectively.The level of ACE,AngⅡ,cTnⅠin patients with DD genotype was significantly higher than the ID andⅡgenotype(P【 0.05).Besides,the level of ACE,AngⅡin patients with ID genotype was significantly higher than the II(P【 0.05).Conclusions:There is certain correlation between CPB perioperative midterm ACE and cTnⅠ,Myo,CK-MB.ACE DD genotype is a susceptibility gene of the CPB perioperative myocardial injury.

Study of angiotensin converting enzyme and genotype among Egyptian preeclampsia patients

Preeclampsia is a frequent disorder with reported incidence in pregnancies. In Egypt, it complicates 6%-8% of pregnancies and reaches 15% in referral centers. The renin-angiotensin system activation during the early stages of Preeclampsia proved to be a direct cause. Women carrying the D allele of the ACE-I/D polymorphism have higher measures of uterine artery resistance, which is a marker for development of intrauterine growth retardation and preeclampsia. The maternal syndrome of preeclampsia (PE) during the latter half of pregnancy is believed to result from impaired placentation in early gestation and a failure to develop low resistance uteroplacental circulation. Aim: The aim of this study was to evaluate the association with angiotensin converting enzyme gene polymorphism and changes in its enzyme serum level in preeclamptic patients compared to non preeclamptic control group together with studying the changes in umbilical artery and uterine artery Doppler. Subjects: The study was conducted on 180 pregnant women allocated into two groups having the same inclusion and exclusion criteria except for hypertension and proteinuria;each group comprised of 90 pregnant women with matched age. Methods: Doppler study of umbilical and uterine arteries and the detection of Angiotensin converting gene polymorphism by PCR with Estimation of serum ACE in serum by ELISA technique. Results: The distribution of the ACE-I/D genotypes and allelic frequencies in the present study of polymorphism was 37.8% for the DD, 48.9% for the ID, 13.3% for the II in preeclampsia group while it was 33.3% for the DD, 46.7% for the ID, and 20% for the II in the control group. There was no significant difference between cases and controls regarding the cumulative D effect. Conclusions: No existence of a relation between preeclampsia and ACE gene polymorphism considering different modes of inheritance whether is dominance or recessiveness. No effect of ACE gene polymorphism is on ACE serum level. Positive correlation between ACE gene polymorphism and the uterine artery Doppler changes gives strong evidence that ACE gene may have a role in the histopathological changes taking place in these vessels, therefore affecting maternal prognosis. It is unclear to explain this mismatched ACE genetic influence on the incidence of preeclampsia, but the multifactorial pathogenesis of the development and complication in preeclampsia and also physician’s intervention may contribute to the pregnancy outcome. Recommendations: International collaborations, particularly among countries with a high incidence of preeclampsia, may help to include participants with different cultural and genetic backgrounds, which can provide further insight into the etiology of the disease both genetic and environmental.

Angiotensin Converting Enzyme as a Possible Biomarker to Predict Effect of Obstetric Anesthesia on Pregnant Women with COVID-19 Infection

We retrospectively investigated 68 parturients with or without COVID-19 undergone emergency cesarean section with combined spinal-epidural anesthesia(CSEA)from a single tertiary university hospital in Wuhan,China.The cases were divided into 2 groups:patients with COVID-19 pneumonia(Group 1)and cases without COVID-19 pneumonia(Group 2).The patients in Group 1 were later divided into 2 groups:patients with low-angiotensin converting enzyme(ACE)(Group 3)and patients with normal-ACE(Group 4).The ACE levels,blood pressure and anesthesia management between the patients of Group 1 and Group 2,Group 3 and Group 4 were recorded as the primary outcome.The secondary outcome included perioperative symptoms,laboratory parameters and vital signs.Compared with Group 2,the patients in Group 1 had different ACE level and lower blood pressure after CSEA.Compared with Group 4,the patients in Group 3 showed lower SBP after CSEA(127 vs.130 mm Hg,p=0.028),accompanied with more partus matures and younger age(28 vs.32 years,p=0.007).ACE may be a possible biomarker to predict the anesthesia effects on patients with COVID-19 infections undergoing emergency cesarean delivery.

超声预处理时间对金枪鱼皮酶解过程ACE抑制肽释放的影响

以水解度、ACE抑制率为指标,并通过电泳、HPLC、红外光谱(FTIR)、热稳定性分析(DSC)研究不同超声预处理时间对金枪鱼皮酶解过程ACE抑制肽释放的影响。结果表明,酶解5 min后,超声预处理组酶解液的水解度与未处理组呈现显著性差异(p <0.05),并且ACE抑制率均高于未处理组,说明超声预处理可改变金枪鱼皮胶原酶解模式,加快短时酶解过程中ACE抑制肽的快速释放。电泳和HPLC分析表明,随着酶解过程的进行,10 kDa以下小分子组分含量呈现往复增减变化,超声预处理会加速该过程进行,从而提高其释放效率。FTIR和DSC分析可知,超声处理会破坏鱼皮胶原蛋白内部氢键的平衡,使其三螺旋结构松散,更多酶切位点暴露,说明超声处理能促进短时酶解过程ACE抑制肽的快速释放。

大鳞副泥鳅蛋白制备ACE抑制肽的酶解方式研究

为开发大鳞副泥鳅蛋白血管紧张素转化酶(angiotensin converting enzyme,ACE)抑制肽,使用高效液相色谱法测定大鳞副泥鳅蛋白的氨基酸组成,考察泥鳅蛋白的单一酶解方式和复合酶解方式对产生ACE抑制肽的影响,并使用N-三(羟甲基)甲基甘氨酸十二烷基硫酸钠-聚丙烯酰胺凝胶电泳进一步证实不同酶解方式对泥鳅蛋白的水解效果。结果表明,大鳞副泥鳅蛋白富含疏水性氨基酸(39.823%)、支链氨基酸(18.102%)以及芳香族氨基酸(8.216%),是制备ACE抑制肽的良好来源。脯氨酸蛋白酶、α-胰凝乳蛋白酶和碱性蛋白酶单一酶解泥鳅蛋白,酶解产物的最高ACE抑制率分别是81.01%、64.91%和87.84%,最高水解度分别为1.48%、9.04%和28.29%。使用碱性蛋白酶与脯氨酸蛋白酶对大鳞副泥鳅蛋白进行分步酶解与同步酶解,同步酶解方式可以产生更高活性的ACE抑制肽,最高的ACE抑制率为90.14%,IC50为0.491 mg/mL。

食源性血管紧张素转换酶抑制肽的研究进展

高血压全球发病率逐年攀升,开发具有抗高血压功效的多肽类食品及保健品将在未来高血压的防治中起重要作用。血管紧张素转换酶是体内血压调控的重要分子,研究开发其抑制肽可安全、有效防控高血压。食物来源的多肽因其安全性高,来源广泛而被学者广泛关注,近年来研究者已经从植物、动物、海洋生物、乳品及发酵制品中发现多种具有抗高血压活性的血管紧张素转换酶抑制肽,然而对功效的验证大多停留在体外实验阶段,仅对少数血管紧张素转换酶抑制肽开展了体内功效研究。

Cytoplasmic domain and enzymatic activity of ACE2 are not required for PI4KB dependent endocytosis entry of SARS-CoV-2 into host cells

The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(ACE2).Here,by using lentivirus based pseudotypes bearing spike protein,we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis,and phosphoinositides played essential roles during this process.In addition,we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry.Finally,we showed that the current predominant Delta variant,although with high infectivity and high syncytium formation,also entered cells through clathrin-mediated endocytosis.These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.

Cardiomyopathy protection in Chagas Disease

There is some published evidence suggesting micro vascular endothelial dysfunction and dysautonomia involvement in Chagas disease in association with cardiomyocyte changes favoring disease progression. The combined treatment between angiotensin converting enzyme (ACE) inhibitor drugs;Simvastatin, muscarinic antibody immunoadsorbent together with fungicidal drugs would open therapeutic possibilities in this disease.